Erythrocyte-bound (Ca2 ion - Mg2 ion)-ATPase has been implicated in the abnormal accumulation of calcium in sickle cells. In this work, the enzyme and its stimulator, calmodulin, have been partially purified from SS, AS, and AA cells in an attempt to determine the specific site of the defect. The results indicate that calmodulin, regardless of the cell type of origin, can stimulate (Ca ion 2 - Mg ion 2)-ATPase from AA cells, but the enzyme from SS cells has reduced activity which is not significantly stimulated by calmodulin.